Background/Objectives: Up to 30% of patients with breast cancers will develop brain or leptomeningeal metastases, and this risk is especially high with HER2-positive cancers. For patients with central nervous system metastases, cerebrospinal fluid (CSF) liquid biopsies are a promising opportunity to monitor disease, inform treatment, and predict prognosis. This pilot study investigated CSF liquid biopsy analytes from three patients diagnosed with central nervous system metastases based on imaging but not confirmed via clinical cytology. Methods: The detection of cellular analytes with the non-enrichment high-definition single-cell assay (HDSCA3.0) workflow was compared between the CSF and matched peripheral blood (PB) samples. Results: Circulating tumor cells (CTCs) were detected in the CSF but not the PB and were subsequently molecularly characterized using single-cell genomics and targeted multiplexed proteomics to reveal a clonal population of phenotypically heterogeneous cells. There was a lack of concordance in the copy number alteration profiles between CTCs and cell-free DNA (cfDNA) in the CSF. Extracellular vesicle surface marker analysis in CSF revealed a prominent signal among tetraspanins (CD9/CD63/CD81), with CD81 exhibiting the highest signal across all patients. Conclusions: The data presented suggest that CSF could be a useful tool for diagnosing and assessing disease severity.
背景/目的：高达30%的乳腺癌患者会发生脑或软脑膜转移，其中HER2阳性癌症患者的风险尤为突出。对于中枢神经系统转移患者，脑脊液液体活检为疾病监测、治疗指导及预后预测提供了重要契机。本项探索性研究对三名经影像学诊断但未通过临床细胞学确认的中枢神经系统转移患者的脑脊液液体活检分析物进行了研究。方法：采用非富集高清晰度单细胞检测技术流程，对脑脊液与匹配的外周血样本中的细胞分析物检测结果进行比较。结果：在脑脊液中检测到循环肿瘤细胞，而外周血中未检出；随后通过单细胞基因组学与靶向多重蛋白质组学进行分子表征，揭示了表型异质性细胞的克隆群体。脑脊液中循环肿瘤细胞与游离DNA的拷贝数变异谱存在不一致性。脑脊液细胞外囊泡表面标志物分析显示四跨膜蛋白家族信号显著，其中CD81在所有患者中均呈现最高信号强度。结论：本研究数据表明，脑脊液检测可作为疾病诊断与严重程度评估的有效工具。
肿瘤(癌症)患者之家